Results from the NIMH Collaborative Depression Study (CDS) have clearly shown that affective illness is a lifetime disorder and that long-term observation will be necessary to adequately characterize it. Follow-up so far shows high rates of recovery, recurrence, changes in inter- episode psychosocial functioning, co-morbid alcoholism, minor affective syndromes, mortality and suicide. Recoveries are likely even after lengthy periods of illness, the distribution of episode length is relatively constant and unimpaired psychosocial functioning appears to require a complete absence of symptoms. It is essential that this follow-up continue, especially as the probands enter their sixth an seventh decades of life. This application seeks to extend the prospective annual follow-up of the CDS proband sample to at least 22 years for all subjects. The genera aim in doing this is to describe the long-term cause of the affective disorders. The specific aims are to collect data that will describe more fully: 1.) the cumulative probability of recovery and recurrence, and the changes in polarity, severity, and episode and cycle lengths; 2.) the predictors of long-term course and diagnostic change; 3.) the eventual level of psychosocial functioning, physical health, likelihood of suicide and mental health service utilization; 4.) the influence of naturalistically applied treatments as a mediating variable; 5.) the cause and outcomes of subsyndromal stages of affective disorders; and 6.) the long-term inter-relationships of the affective disorders and other chronic and recurrent disorders such as alcohol and drug use disorders.